Structures of human pannexin 1 reveal ion pathways and mechanism of gating.

ABSTRACT: Pannexin 1 (PANX1) is an ATP-permeable channel with critical roles in a variety of physiological functions such as blood pressure regulation¹, apoptotic cell clearance² and human oocyte development³. Here we present several structures of human PANX1 in a heptameric assembly at resolutions of up to 2.8 angström, including an apo state, a caspase-7-cleaved state and a carbenoxolone-bound state. We reveal a gating mechanism that involves two ion-conducting pathways. Under normal cellular conditions, the intracellular entry of the wide main pore is physically plugged by the C-terminal tail. Small anions are conducted through narrow tunnels in the intracellular domain. These tunnels connect to the main pore and are gated by a long linker between the N-terminal h

SUBMITTER: Ruan Z 

PROVIDER: S-EPMC7814660 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature